title: Bleeding and risk of death with hydroxyethyl starch in severe sepsis: post hoc analyses of a randomized clinical trial.
abstract: OBJECTIVE
  We aimed to characterize the degree and clinical importance of bleeding in patients treated with hydroxyethyl starch (HES).
  
  
  METHODS
  In post hoc analyses, we examined the associations between fluid assignment, hemostatic variables, bleeding events, transfusions, and death among 798 patients with severe sepsis randomized to fluid resuscitation with HES 130/0.42 versus Ringer's acetate. We used Cox regression analysis adjusted for fluid assignment and baseline characteristics.
  
  
  RESULTS
  Overall, 93 (23 %) patients assigned to HES versus 60 (15 %) patients assigned to Ringer's acetate bled in the ICU (relative risk (RR) 1.55; 95 % CI 1.16-2.08; P = 0.003). Of these, 38 and 25 (RR 1.52; 95 % CI 0.94-2.48; P = 0.09), respectively, had severe bleeding (intracranial or concomitant transfusion with three units of red blood cells). Most patients bled in the first days after randomization when most trial fluid was given. The hazards ratios for occurrence of any bleeding and severe bleeding in patients treated with HES versus Ringer's acetate were 1.70 (95 % CI 1.23-2.36; P = 0.001) and 1.55 (95 % CI 0.93-2.56; P = 0.09), respectively. The adjusted hazard ratios for death among patients with any bleeding and severe bleeding compared to those without bleeding were 1.36 (95 % CI 1.04-1.79; P = 0.03) and 1.74 (95 % CI 1.20-2.53; P = 0.004), respectively.
  
  
  CONCLUSIONS
  In post hoc analyses of patient with severe sepsis, treatment with HES increased the risk of bleeding which was associated with increased risk of death. HES-induced bleeding complications may negatively affect outcome in patients with severe sepsis.
authors.affiliation: Department of Intensive Care, Copenhagen University Hospital, Rigshospitalet, 2100, Copenhagen, Denmark, nicolai.rosenkrantz.segelcke.haase@regionh.dk.
authors.forename: Nicolai
authors.initials: N
authors.lastname: Haase
authors.forename: Jørn
authors.initials: J
authors.lastname: Wetterslev
authors.forename: Per
authors.initials: P
authors.lastname: Winkel
authors.forename: Anders
authors.initials: A
authors.lastname: Perner
mesh_terms: D000368:Aged; D004311:Double-Blind Method; D017707:Erythrocyte Transfusion; D005260:Female; D005440:Fluid Therapy; D006454:Hemoglobins / Q000378:metabolism; D006470:Hemorrhage / Q000139:chemically induced* / Q000401:mortality* / Q000628:therapy; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives / Q000009:adverse effects*; D007552:Isotonic Solutions / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D012044:Regression Analysis; D018805:Sepsis / Q000188:drug therapy* / Q000401:mortality
chemical_list: D006454:Hemoglobins; D006895:Hydroxyethyl Starch Derivatives; D007552:Isotonic Solutions; C028570:Ringer's acetate